Study of mechanisms of antipsychotic-induced metabolic disturbances: potential for application of cellular models

The therapy with antipsychotic drugs (AD) of the first and second generations is accompanied by metabolic side effects. The papers of recent years have revealed both central (induction of resistance to the satiety hormone leptin, change in level of adiponectin suppressing glyconeogenesis and elevating sensitivity of cells to insulin) and peripheral (activation of system of sterol regulatory element-binding proteins (SREBPs), performing transcription of genes of cholesterol and fatty acid biosynthesis along with inhibition of late phases of synthesis of cholesterol as well as change in intracellular cholesterol transport) mechanisms of realization of antipsychotic-induced metabolic disturbances. The study of the interrelationship between emergence of metabolic disturbances under therapy with AD and changes in production of cytokines and other inflammation factors is promising. A part of such studies as well as studies of peripheral mechanisms of side effects of AD can by efficiently performed in vitro on the models of cultivated cells, first of all, hepatogenic ones.